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M. Okumura



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    MINI 28 - Psychological Impact of Lung Cancer and its Treatment (ID 150)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Palliative and Supportive Care
    • Presentations: 1
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      MINI28.10 - C-Type Natriuretic Peptide Attenuates Bleomycin-Induced Fibrosis and Inflammation in Murine Lung (ID 471)

      16:45 - 18:15  |  Author(s): M. Okumura

      • Abstract
      • Presentation
      • Slides

      Background:
      Interstitial lung diseases (ILDs) are sometimes seen in patients with primary lung cancer. Therapeutic interventions for lung cancer patients with ILDs occasionally induce acute exacerbation (AE), which is a potentially fatal complication. However, no prophylactic treatments have been established. Although the etiology of ILD-related AE is unknown, management of the ILD disease process, including fibrotic changes and inflammatory reactions, is thought to lead to the prophylaxis of AE. C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family, which includes atrial and brain natriuretic peptides. CNP has cardioprotective effects, such as anti-fibrotic and anti-inflammatory effects, in animal models of myocarditis and myocardial infarction. The objective of the present study was to investigate the anti-fibrotic and anti-inflammatory effects of CNP on bleomycin (BLM)-induced lung injury.

      Methods:
      C57BL/6 mice were divided into two groups, vehicle- and CNP-treated groups, for evaluation of pulmonary fibrosis and inflammation induced by BLM. CNP (2.5 µg/kg/min) or vehicle were subcutaneously infused using an osmotic mini-pump from 24 h before BLM administration until the mice were euthanized. On 14 days after intratracheal administration of BLM (1 mg/kg), histological changes, collagen content, and mRNA expression of inflammatory cytokines in lungs and bronchoalveolar lavage fluid (BALF) were assessed.

      Results:
      Continuous infusion of CNP attenuated BLM-induced fibrotic changes. Quantitative histological analysis showed that BLM-induced fibrotic lesions were significantly smaller in CNP treated mice compared to vehicle mice. The collagen content, determined with the hydroxyproline assay, increased in BLM-administered lung and CNP treatment reduced BLM-induced collagen production. CNP treatment tended to improve body weight loss after BLM administration. In BALF, BLM administration augmented the number of inflammatory cells in the vehicle group, which was significantly lower in CNP treated mice. The expression of IL-1β, IL-6, and bFGF mRNA were significantly elevated by BLM administration, and CNP treatment significantly attenuated these increases. Figure 1



      Conclusion:
      These results indicate that CNP attenuates fibrotic changes, namely the accumulation of inflammatory cells, and the increased expression of inflammatory cytokines in BLM-induced pulmonary fibrosis. CNP may have therapeutic potential in patients with ILD and lead to prophylaxis for AE.

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    P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      P1.02-005 - Impact of Postoperative Complications on Cancer Recurrence following Lung Cancer Surgery (ID 477)

      09:30 - 17:00  |  Author(s): M. Okumura

      • Abstract
      • Slides

      Background:
      Recent studies indicate that postoperative complications after various types of cancer surgery are associated with poor cancer-specific survival. Postoperative complications induce severe inflammatory reaction during the perioperative period. Emerging evidence suggests that systemic inflammation can accelerate the adhesion of circulating tumor cells to the vascular endothelium of distant organs, which is the first step of extravasation in hematogenous metastasis. The objective of this study was to investigate the impact of postoperative cardiopulmonary complications on cancer recurrence after lung cancer surgery.

      Methods:
      From a prospective database of 675 consecutive patients who underwent a lung cancer surgery between April 2007 and March 2012, we retrospectively analyzed medical charts of all patients with curative surgery. The primary endpoint was the incidence of cancer recurrence after surgery between the patients with and without postoperative cardiopulmonary complications. Perioperative white blood cell counts and C-reactive protein levels were also compared.

      Results:
      Postoperative cardiovascular or respiratory complications were identified in 98 (15%) or 30 (4%) patients, respectively. There were no significant differences in the incidence of cancer recurrence between the patients with postoperative cardiovascular complications and without cardiopulmonary complications (23% vs. 19%; p = 0.26). In contrast, there was significantly higher incidence of cancer recurrence in those with postoperative respiratory complications than those without cardiopulmonary complications (42% vs. 19%; p < 0.05). Multiple regression analysis adjusted age, sex, and pathological staging showed the similar tendency, however there was no significant difference. There were significantly higher levels of white blood cell counts and C-reactive protein levels in the acute phase after surgery in those with postoperative respiratory complications than those without. Figure 1



      Conclusion:
      Not cardiovascular but respiratory complications following lung cancer surgery might have the negative predictor in the incidence of cancer recurrence. Severe inflammation induced by postoperative complications might be associated with high incidence of cancer recurrence.

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